Ethylene Oxide → HCID 71509091, compound

HRID 1499929Notes

Reaction equation

HRID 1499929 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=O.F[C:9](F)(F)[C:10]([OH:12])=O.[NH2:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]2[N:22]([CH:26]([C:28]3[CH:35]=[C:34](C)[C:31]([C:32]#[N:33])=[C:30]([CH:37]4CNC4)[C:29]=3OCC)[CH3:27])[N:23]=[C:24]([CH3:25])[C:17]=12.C[CH2:45][N:46](C(C)C)[CH:47](C)C.O1[CH2:55][CH2:54]1.O1CCC[CH2:57]1>>[NH2:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]2[N:22]([CH:26]([C:28]3[CH:29]=[C:30]([CH3:37])[C:31]([C:32]#[N:33])=[C:34]([CH:55]4[CH2:54][N:46]([CH2:47][C:10]([OH:12])([CH3:9])[CH3:57])[CH2:45]4)[C:35]=3[O:5][CH2:3][CH3:2])[CH3:27])[N:23]=[C:24]([CH3:25])[C:17]=12

Participants

5

Reactant 4

HCID 6354Ethylene OxideHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 86677847HCID 86677847, compound2×

Product 1

HCID 71509091HCID 71509091, compoundYield 50%

Conditions

Temperature
95 °C

Procedure

The 4-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-2-azetidin-3-yl-3-ethoxy-6-methylbenzonitrile (0.055 g, 0.14 mmol, chiral intermediate from Example 320, Step 1) was combined with tetrahydrofuran (22 mL), DIPEA (0.049 mL, 0.28 mmol) and oxirane, 2,2-dimethyl-(0.018 mL, 0.21 mmol) at room temperature. The reaction was heated to 95° C. and allowed to stir overnight. The reaction was allowed to cool to room temperature and was purified without workup by prep HPLC on a C-18 column eluting water:acetonitrile gradient buffered pH 10 to give the title compound as a white amorphous solid (0.035 g, 50%). The product was isolated as a single enantiomer. LCMS calculated for C25H34N7O2(M+H)+: m/z=464.3; found: 464.3. 1H NMR (300 MHz, DMSO-d6) δ 8.09 (s, 1H), 7.23 (s, 1H), 6.21 (q, J=6.8 Hz, 1H), 4.00 (m, 4H), 3.81-3.54 (m, 2H), 3.15 (m, 2H), 2.53 (s, 3H), 2.33 (s, 3H), 2.27 (bs, 2H), 1.70 (d, J=7.1 Hz, 3H), 1.30 (t, J=6.9 Hz, 3H), 1.04 (s, 6H).

Workup

  1. temperatureto cool to room temperature
  2. customwas purified without workup by prep HPLC on a C-18 column
  3. washeluting water

Sources & evidence

ORD record
ord-309fd9814f074c3da53a5db8f261ae3c
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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